COVID-19 vaccine hesitancy among patients in two urban emergency departments.
Widespread vaccination is an essential component of the public health response to the COVID-19 pandemic, yet vaccine hesitancy remains pervasive. This prospective survey investigation aimed to measure the prevalence of vaccine hesitancy in a patient cohort at two urban emergency departments (EDs) and characterize underlying factors contributing to hesitancy. Adult ED patients with stable clinical status (Emergency Severity Index 3-5) and without active COVID-19 disease or altered mental status were considered for participation. Demographic elements were collected as well as reported barriers/concerns related to vaccination and trusted sources of health information. Data were collected in person via a survey instrument proctored by trained research assistants. A total of 1,555 patients were approached, and 1,068 patients completed surveys (completion rate = 68.7%). Mean (±SD) age was 44.1 (±15.5) years (range = 18-93 years), 61% were female, and 70% were Black. A total of 31.6% of ED patients reported vaccine hesitancy. Of note, 19.7% of the hesitant cohort were health care workers. In multivariable regression analysis, Black race (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.62 to 6.85) and younger age (age 18-24 years-OR = 4.57, 95% CI = 2.66 to 7.86; age 25-35 years-OR = 5.71, 95% CI = 3.71 to 8.81) were independently associated with hesitancy, to a greater degree than level of education (high school education or less-OR = 2.27, 95% CI = 1.23 to 4.19). Hesitant patients were significantly less likely to trust governmental sources of vaccine information than nonhesitant patients (39.6% vs. 78.9%, p < 0.001); less difference was noted in the domain of trust toward friends/family (51.1% vs. 61.0%, p = 0.004). Hesitant patients also reported perceived vaccine safety concerns and perceived insufficient research. Vaccine hesitancy is common among ED patients and more common among Black and younger patients, independent of education level. Hesitant patients report perceived safety concerns and low trust in government information sources but less so friends or family. This suggests that strategies to combat hesitancy may need tailoring to specific populations.


Defining the native disulfide topology in the somatomedin B domain of human vitronectin.
The N-terminal 44 amino acid residues of the human plasma glycoprotein vitronectin, known as the somatomedin B (SMB) domain, mediates the interaction between vitronectin and plasminogen activator inhibitor 1 (PAI-1) in a variety of important biological processes. Despite the functional importance of the Cys-rich SMB domain, how its four disulfide bridges are arranged in the molecule remains highly controversial, as evidenced by three different disulfide connectivities reported by several laboratories. Using native chemical ligation and orthogonal protection of selected Cys residues, we chemically synthesized all three topological analogs of SMB with predefined disulfide connectivities corresponding to those previously published. In addition, we oxidatively folded a fully reduced SMB in aqueous solution, and prepared, by CNBr cleavage, the N-terminal segment of 51 amino acid residues of intact vitronectin purified from human blood. Proteolysis coupled with mass spectrometric analysis and functional characterization using a surface plasmon resonance based vitronectin-PAI-1-SMB competition assay allowed us to conclude that 1) only the Cys(5)-Cys(21), Cys(9)-Cys(39), Cys(19)-Cys(32), and Cys(25)-Cys(31) connectivity is present in native vitronectin; 2) only the native disulfide connectivity is functional; and 3) the native disulfide pairings can be readily formed during spontaneous (oxidative) folding of the SMB domain in vitro. Our results unequivocally define the native disulfide topology in the SMB domain of human vitronectin, providing biochemical as well as functional support to the structural findings on a recombinant SMB domain by Read and colleagues (Zhou, A., Huntington, J. A., Pannu, N. S., Carrell, R. W., and Read, R. J. (2003) Nat. Struct. Biol. 10, 541-544).


Mouse cachexia induced by trehalose dimycolate from Nocardia asteroides.
Trehalose dimycolate (TDM) isolated from Nocardia asteroides induced in mice a severely wasted condition known as cachexia. Intraperitoneal injection of mice with five 10 micrograms doses of TDM in mineral oil at intervals of 2 d killed 90% of the animals within 26 d. Death followed a precipitous weight loss and an inflammatory process in the peritoneal cavity. When mice were injected intraperitoneally with a single 10 micrograms dose of TDM, 48 h later, they had begun to lose weight and exhibited extreme hypertriglyceridaemia and hypoglycaemia. Tumour necrosis factor (or cachectin) was detected in the plasma from animals injected with TDM. This cytokine released by mononuclear phagocytes may be involved in the induction of cachexia by TDM.


Macrocephaly and bitemporal arachnoid cysts not associated with glutaric aciduria type I in a child.
A 45-month-old child who had bitemporal arachnoid cysts and macrocephaly unrelated to glutaric aciduria type 1 (GA 1) was reported. The patient was admitted to the emergency unit after head trauma at 11 months of age. CT and MRI showed bitemporal arachnoid cysts (BACs). Acylcarnitine profile was normal in serum using tandem mass spectrometry. Urine and blood screening tests were within normal range for metabolic disorders. There were no unusual organic acids in urine and blood samples. No additional clinical findings of metabolic disorders such as GA 1 developed during follow-up. The majority of children affected with GA 1 have macrocephaly and BACs on CT or MRI. These signs should alert neurosurgeons to the possibility of GA 1. Neurosurgeons evaluating patients with head trauma or suspected non-accidental head injury should include GA 1 in the differential diagnosis of BACs associated with macrocephaly, and an evaluation should be performed.


Validation of the German Normalisation Process Theory Measure G-NoMAD: translation, adaptation, and pilot testing.
Implementing evidence-based healthcare practices (EBPs) is a complex endeavour and often lags behind research-informed decision processes. Understanding and systematically improving implementation using implementation theory can help bridge the gap between research findings and practice. This study aims to translate, pilot, and validate a German version of the English NoMAD questionnaire (G-NoMAD), an instrument derived from the Normalisation Process Theory, to explore the implementation of EBPs. Survey data has been collected in four German research projects and subsequently combined into a validation data set. Two versions of the G-NoMAD existed, independently translated from the original English version by two research groups. A measurement invariance analysis was conducted, comparing latent scale structures between groups of respondents to both versions. After determining the baseline model, the questionnaire was tested for different degrees of invariance (configural, metric, scalar, and uniqueness) across samples. A confirmatory factor analysis for three models (a four-factor, a unidimensional, and a hierarchical model) was used to examine the theoretical structure of the G-NoMAD. Finally, psychometric results were discussed in a consensus meeting, and the final instructions, items, and scale format were consented to. A total of 539 health care professionals completed the questionnaire. The results of the measurement invariance analysis showed configural, partial metric, and partial scalar invariance indicating that the questionnaire versions are comparable. Internal consistency ranged from acceptable to good (0.79 ≤ α ≤ 0.85) per subscale. Both the four factor and the hierarchical model achieved a better fit than the unidimensional model, with indices from acceptable (SRMR = 0.08) to good (CFI = 0.97; TLI = 0.96). However, the RMSEA values were only close to acceptable (four-factor model: χ2164 = 1029.84, RMSEA = 0.10; hierarchical model: χ2166 = 1073.43, RMSEA = 0.10). The G-NoMAD provides a reliable and promising tool to measure the degree of normalisation among individuals involved in implementation activities. Since the fit was similar in the four-factor and the hierarchical model, priority should be given to the practical relevance of the hierarchical model, including a total score and four subscale scores. The findings of this study support the further usage of the G-NoMAD in German implementation settings. Both the AdAM project (No. NCT03430336, 06/02/2018) and the EU-project ImpleMentAll (No. NCT03652883, 29/08/2018) were registered on ClinicalTrials.gov. The ImplementIT study was registered at the German Clinical Trial Registration (No. DRKS00017078, 18/04/2019). The G-NoMAD validation study was registered at the Open Science Framework (No7u9ab, 17/04/2023).


Comparison of expression of cathepsins B and L and MMP2 in endothelial cells and in capillary sprouting in collagen gel.
The lysosomal cysteine proteinases cathepsins B and L are known to play an important role in the invasive growth of tumor cells, but their association with angiogenesis has been less well studied. The aim of this study was to determine the possible role of endothelial cell-associated cathepsins B and L in induced capillary growth in the aorta ring model of angiogenesis. Specific inhibitors of cysteine proteinases did not inhibit capillary growth in aorta ring culture and only slightly inhibited the degradation of surrounding collagen. In contrast, strong inhibition of both processes by the matrix metalloproteinase inhibitor BB-94 was observed, indicating the importance of endogenous MMP production in angiogenesis. In support of this finding, we demonstrated a significant increase in endogenous endothelial mRNA of MMP2, but not of cathepsins B and L, in proliferating primary human dermal microvascular endothelial cells (HMVEC-d) in culture. However, MMP2 mRNA expression was increased only when the cells were embedded in collagen but not when they were grown on plastic, regardless of the addition of the growth factors VEGF or bFGF. Moreover, on plastic the impairment of MMP2 induction by growth factors was observed. The differential effect of growth factors implies the crosstalk with integrin signaling as a consequence of binding to the different matrix. This study suggests that endothelial cell-associated cathepsins B and L are not involved in the invasive growth of capillaries from existing blood vessels and that the presence of collagen is necessary for MMP2 expression in endothelial cells.


Evaluation of dosimetry of radioiodine therapy in benign and malignant thyroid disorders by means of iodine-124 and PET.
The aim of this study was to evaluate the use of 124I positron emission tomography (PET) to determine the dosimetry of radioiodine therapy in hyperthyroidism and thyroid cancer. Phantom studies to assess the accuracy of PET were performed using an EEC phantom with spheres of different diameters filled with 3-30 MBq of 124I. Patient dosimetry was derived from PET data obtained 1-13 days after simultaneous oral administration of a therapeutic dose of 131I and a diagnostic dose of 124I. The obtained data were compared with findings from intratherapeutic probe measurements and clinical outcome. The phantom studies confirmed that 124I can be quantitated by PET (imprecision < or =10%), and volumetry is feasible for nodules <13 mm (imprecision < or =20%). Any influence of contamination with 123I or the simultaneous administration of 131I on the accuracy of the PET quantification and the probe measurements was ruled out by phantom measurements with solutions of 131I, 124I and 123I in various ratios. In autonomous nodular goitres, radioiodine uptake measured by PET varied from 25.4% to 64.3% and was not significantly different from that obtained by a scintillation probe (24.1%-73.1%, correlation coefficient r=0.91). Comparison of uptake and effective half-life in normal tissue versus autonomous nodules revealed significant differences in uptake but not in effective half-life [uptake 2.0-8.3 kBq/(ml x MBq) in normal tissue vs 12.6-29.3 kBq/(ml x MBq) in nodules; half-life 97.8-156.7 h in normal tissue vs 73.3-192.3 h in nodules]. Calculated radiation doses ranged between 177 and 633 Gy for autonomous nodules and between 47 and 126 Gy for normal tissue. In thyroid cancer patients, doses between 350 and 1,420 Gy were achieved in thyroid remnants and between 70 and 170 Gy in tumour metastases. It is concluded that 124I and PET are suitable for evaluation of the dosimetry of radioiodine therapy in benign and malignant thyroid diseases. The applied technique might be particularly useful for quantitative dose-response studies in radioiodine treatment and further investigations of stunning phenomena.


The U.S. military's Neisseria gonorrhoeae resistance surveillance initiatives in selected populations of five countries.
Multi-drug resistant Neisseria gonorrhoeae (GC) threatens the successful treatment of gonorrhea. This report presents preliminary findings with regard to the prevalence of laboratory-confirmed GC and the extent of drug-resistance among sample populations in five countries. Between October 2010 and January 2013, 1,694 subjects (54% male; 45% female; 1% unknown) were enrolled and screened for the presence of laboratory-confirmed GC in the United States, Djibouti, Ghana, Kenya, and Peru. Overall, 108 (6%) of enrolled subjects tested positive for GC. Antimicrobial susceptibility testing results were available for 66 GC isolates. Resistance to at least three antibiotics was observed at each overseas site. All isolates tested in Ghana (n=6) were resistant to ciprofloxacin, penicillin, and tetracycline. In Djibouti, preliminary results suggested resistance to penicillin, tetracycline, ciprofloxacin, cefepime, and ceftriaxone. The small sample size and missing data prevent comparative analysis and limit the generalizability of these preliminary findings.


[Effect of 5-aminolevulinic Acid Photodynamics Therapy on Biofilm of Propionibacterium Acnes].
Objective To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on Propionibacterium acnes (P.acnes) biofilm. Methods P.acnes biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm2),ALA-PDT2 group (100 J/cm2),ALA-PDT3 group (200 J/cm2)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. Results CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(md=0.003, P=1.000)and LED group(md=-0.025, P=1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (md=-0.162, P<0.001),ALA-PDT2 group (md=-0.254, P<0.001),and ALA-PDT3 group (md=-0.352, P<0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(md=-0.044, P=1.000)and LED groups (md=-0.020, P=1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (md=1.175, P<0.001),ALA-PDT2 group (md=1.942, P<0.001),and ALA-PDT3 group (md=-0.352, md=2.742, P<0.001). Conclusions ALA-PDT has an inhibitory effect on P.acnes biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.


[The current clinical spectrum of pulmonary thromboembolism].
BACKGROUND. Mortality in pulmonary thromboembolism (PTE) decreases considerable when it is diagnosed early. The suspicion based on clinical and complementary data is essential for an early diagnosis. METHODS. Retrospective review of the clinical features in patients diagnosed of PTE in an Internal Medicine department from January 1993 to December 1999. RESULTS. A total of 117 patients with PTE were identified. The median age was 68.8 years. Sixty-six patients (56.4%) had one or more risk factors for PTE. The most common risk factor was immobilization (37.6%). Dyspnea was the most common symptom (74.4%) and tachypnea the most common sign (66.7%). Fever/low grade fever and leukocytosis were present in 16.2% and 31.6% of patients, respectively. Respiratory failure, alkalosis and hypocapnia were present in 44.4%, 38.5% and 47% of patients, respectively. An alveolar-arterial oxygen gradient > 20 mmHg was demonstrated in 96.6% of patients. Chest radiographs and electrocardiograms were normal in 52.1% and 23.9% of patients, respectively. A vein echo-duplex of the lower limbs demonstrated deep vein thrombosis (DVT) in 52.1% of patients. The hospital mortality rate was 6.8%. CONCLUSIONS. PTE still affects older patients mainly and frequently known risk factors are not detected. The presence of fever/low grade fever and/or leukocytosis does not rule out PTE. Both chest radiographs and electrocardiograms may be normal. Not demonstrating DVT in the lower limbs by the vein echo-duplex does not rule out PTE. The hospital mortality rate has not decreased considerably in the last few years.


Pseudomonas ovata sp. nov., Isolated from the Skin of the Tail of Farmed Murray cod (Maccullochella peelii peelii) with a Profound Ulceration.
A Gram-negative, strictly aerobic, motile, rod-shaped bacterium with monopolar flagellum, designated as F51T, was isolated from the skin ulcer of farmed Murray cod sampled from Zhejiang Province, China. Strain F51T grew at 4-37 °C (optimal temperature, 28 °C), pH 5.0-8.5 (optimal pH, 7.5) and NaCl concentration of 0-6.0% (w/v) (optimal concentration, 2.0%). Phylogenetic analysis based on average nucleotide identity (76.2-78.4%) and in silico DNA-DNA hybridization (22.3-23.2%) values revealed that strain F51T forms a distinct lineage in the clade of genus Pseudomonas with less than 98.9% 16S rRNA gene sequence similarity to type strains of the genus and represents a novel species related most closely to Pseudomonas floridensis LMG 30013T. Three housekeeping genes (rpoB, rpoD and gyrB) of strain F51T were analysed to further confirm that the isolate is distinctly delineated from related Pseudomonas species. Chemotaxonomic analysis indicated that the sole respiratory quinone of strain F51T is Q-9; its predominant cellular fatty acids are C16:0, summed feature 3 (iso-C15:0 2-OH and/or C16:1ω7c), summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C10:0 3-OH; and its major polar lipids consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified glycolipids, three unidentified phospholipids and an unidentified aminophosphoglycolipid. This composition is typical of the chemotaxonomic attributes of Pseudomonas. Based on its phenotypic, chemotaxonomic and phylogenetic features, strain F51T is considered to represent a novel species for which the name Pseudomonas ovata sp. nov. is proposed. The type strain is F51T (= KCTC 62133T = MCCC 1K03458T).


How atopic is atopic dermatitis?
The extent to which the phenotype of atopic dermatitis (AD) is truly atopic has been the subject of much debate. We sought to systematically evaluate the evidence for the value of measurement of IgE antibodies in diagnosing AD and whether knowledge of IgE sensitization increases clinical diagnostic and predictive ability. We searched Medline from its inception until September 2003. Only studies that measured atopy as either skin prick test positivity or IgE-antibody sensitization to environmental allergens were included within a descriptive analysis. Because the small number of studies of adequate quality did not allow a formal meta-analysis, we assigned strength of evidence according to predefined quality criteria and ranked studies accordingly. Inclusion of atopy as part of the diagnostic criteria for AD did not enhance the criteria's sensitivity and specificity in relation to the clinical phenotype of AD. The strength of association between atopy and AD varied significantly between hospital studies (47% to 75%; n=14 studies) and was stronger in hospital than in community populations (7.4% to 78%; n=13 studies). Whereas study quality did not have an effect on atopy prevalence in hospital populations, low atopy prevalences in community surveys were seen in less rigidly conducted studies. AD severity was positively associated with the number of positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that measured both. Only one study suggested that IgE-specific sensitization to hen's egg is associated with subsequent development of AD, and 2 studies found that allergen-specific IgE sensitization in patients with AD is a prognostic marker for allergic airway disease in later life. Atopy-associated AD might also have a worse long-term prognosis than AD that is not associated with atopy. Although atopy is clearly associated with AD, the role of IgE sensitization in AD needs further study. Current evidence suggests that up to two thirds of persons with AD are not atopic, which implies that continued use of the term atopic dermatitis is problematic. Longitudinal studies are needed to compare the treatment response and prognosis of IgE-associated and non-IgE-associated AD.


Excess lung cancer occurrence in poultry plants. Occupational risk factors: Findings for oncogenic viruses exposure and other occupational exposures.
Certain viruses naturally infect and cause cancer in chickens and turkeys. Humans are widely exposed. The viruses cause cancer in primates, and transform human cells in vitro, but it is not known if they cause cancer in humans, mainly because of the lack of epidemiologic evidence. We conducted cohort mortality studies of workers in poultry slaughtering/processing plants across the United States, because they have the highest human exposures. An excess of lung cancer and other deaths was recorded in the poultry workers. Here, we report on a case-cohort study of the lung cancer deaths nested within these cohorts, that was conducted to provide epidemiologic evidence linking these viruses with human cancer occurrence, while adjusting for possible confounders, including workplace chemical carcinogens. We obtained interviews for 339 lung cancer deaths and 457 controls, selected from our combined cohorts of 30,411 poultry plant workers and 16,405 non-poultry workers, belonging to United Food & Commercial Workers unions. Data was analyzed by both logistic regression and Cox regression, adjusting for smoking and other confounders. Lung cancer risk was independently associated with tasks or work areas indicative of exposure to both poultry oncogenic viruses and to workplace chemical carcinogens. The study provides an incremental piece of evidence (epidemiologic), indirectly linking the oncogenic viruses of poultry with the occurrence of cancer in humans, and thus may have public health implications, but the limitations highlighted must be considered. Confirmatory studies, particularly molecular studies providing definitive proof of poultry oncogenic retrovirus integration in human DNA are needed, before the findings observed in this study can be put into proper perspective.


A New Approach for Advertising CTR Prediction Based on Deep Neural Network via Attention Mechanism.
Click-through rate prediction is critical in Internet advertising and affects web publisher's profits and advertiser's payment. The traditional method of obtaining features using feature extraction did not consider the sparseness of advertising data and the highly nonlinear association between features. To reduce the sparseness of data and to mine the hidden features in advertising data, a method that learns the sparse features is proposed. Our method exploits dimension reduction based on decomposition, takes advantage of the attention mechanism in neural network modelling, and improves FM to make feature interactions contribute differently to the prediction. We utilize stack autoencoder to explore high-order feature interactions and use improved FM for low-order feature interactions to portray the nonlinear associated relationship of features. The experiment shows that our method improves the effect of CTR prediction and produces economic benefits in Internet advertising.


[Behavior of cultured cells on the surface of A12O3 ceramics of different consistencies].
The in vitro reactions of mesenchymal cell populations on different powdery and cubical Al2O3 ceramic implants are described compared with those on glass. The ceramics differ because of different compounds and surface processing. The physiologic eluate of the contaminated ceramics induce no cytotoxic and no antiproliverative effect on the single layer population in vitro. The cells settle itself on the ceramic surface. They constidued a confluent cell layer about the whole surface by proliferation (morphogenetic reaction). No difference in the behaviour of the fibroblast-like cells was observed referable to the chemical compound or the surface of the Al2O3 ceramics. The aluminium oxide ceramic presents itself as an absolutely bioinert material despite of strong soiling.


Antiproliferative effects of citrus limonoids against human neuroblastoma and colonic adenocarcinoma cells.
Limonoids, a family of triterpenoids with putative anticancer properties, occur in fruits as glucosides and aglycones. Both highly purified forms were isolated from seeds and molasses of citrus fruits and tested for toxic effects against two human cancer cell lines, SH-SY5Y neuroblastoma and Caco-2 colonic adenocarcinoma, and a noncancerous mammalian epithelial Chinese hamster ovary (CHO) cells. Viability, as quantified by 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium reduction and light microscopy, was shortened significantly (P < 0.001) in cancer cells exposed to aglycones, viz., limonin, nomilin, obacunone, and deacetylnomilin. SH-SY5Y cells were more sensitive than Caco-2 cells to the limonoids, whereas noncancerous CHO cells showed hardly any change in cell numbers or cell morphology. Aglycone toxicity was dose dependent, but below the killing potential of glucosides. This observation correlated with a slower rate of induction of caspase 3/7 activity by aglycones. A flow cytometric analysis of SH-SY5Y cells treated with glucosides and aglycones showed an increased ploidy, which is consistent with enhancing chromosomal abnormalities. The results confirm that limonoids exert a strong multifaceted lethal action against cancer cells, but are relatively ineffective against CHO cells. Of the two, metabolites derived from glucosides are the more likely progenitors of an apoptosis response in situ.


Periostin is expressed by cells of the human and sand rat intervertebral discs.
Periostin, a matricellular protein in the fasciclin family, is expressed in tissues subjected to constant mechanical stress. Periostin modulates cell-to-extracellular matrix interactions and can bind to collagen, fibronectin, tenascin-C and several integrins. Our objective was to evaluate whether periostin is expressed in the human intervertebral disc. Immunohistochemical localization of periostin was carried out in tissue of human lumbar discs and lumbar discs of the sand rat (Psammomys obesus). Human discs also were examined for periostin gene expression. Immunohistochemical localization demonstrated periostin in the cytoplasm of annulus and nucleus cells, and occasionally in the surrounding pericellular and interterritorial extracellular matrix. Periostin distribution in the human disc was distinctive. Outer annulus contained the highest proportion of periostin-positive cells (88.8%), whereas inner annulus contained only 61.4%. The nucleus pulposus contained the fewest periostin-positive cells (18.5%). There was a significant negative correlation between the percentage of cells positive for periostin in the inner annulus and subject age. Periostin gene expression in the human disc also was confirmed using molecular microarray analysis. Because work by others has shown that periostin plays an important role in the biomechanical properties of other connective tissues (skin, tendon, heart valves), future research is needed to elucidate the role of periostin in disc, loading, aging and degeneration.


Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway.
Pharmacological stimulation of adipose tissue remodeling and thermogenesis to increase energy expenditure is expected to be a viable therapeutic strategy for obesity. Berberine has been reported to have pharmacological activity in adipose tissue to anti-obesity, while the mechanism remains unclear. Here, we observed that berberine significantly reduced the body weight and insulin resistance of high-fat diet mice by promoting the distribution of brown adipose tissue and thermogenesis. We have further demonstrated that berberine activated energy metabolic sensing pathway AMPK/SIRT1 axis to increase the level of PPARγ deacetylation, which leads to promoting adipose tissue remodeling and increasing the expression of the thermogenic protein UCP-1. These findings suggest that berberine that enhances the AMPK/SIRT1 pathway can act as a selective PPARγ activator to promote adipose tissue remodeling and thermogenesis. This study proposes a new mechanism for the regulation of berberine in adipose tissue and offers a great prospect for berberine in obesity treatment.


Nocturnal nasal continuous positive airway pressure in patients with chronic obstructive pulmonary disease. Influence on waking respiratory muscle function.
Patients with COPD often have reduced inspiratory muscle strength and endurance as well as poor exercise tolerance. Increased inspiratory work during sleep (probably due to increased upper airway resistance) may further strain these compromised respiratory muscles in COPD patients. We hypothesized that nasal continuous positive airway pressure (CPAP) might reduce respiratory work during sleep in COPD patients and thereby improve waking inspiratory muscle function. To test this hypothesis, eight male COPD patients were treated with sustained nocturnal nasal CPAP. Inspiratory muscle strength (maximum inspiratory pressure) and endurance (sustained inspiratory pressure) as well as clinical performance (12-min walk) were assessed before and after therapy. We observed that compared with matched controls, COPD patients treated with nocturnal nasal CPAP had significant and substantial improvement in inspiratory muscle strength and endurance as well as functional ability as assessed by the 12-min walk. In addition, CPAP did not significantly alter sleep quality or oxygenation in the patients studied. We conclude that nocturnal nasal CPAP improves inspiratory muscle performance during wakefulness in COPD patients, which is very likely a product of the reduced work of breathing during sleep while these individuals received CPAP.


Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome.
Polycystic Ovary Syndrome (PCOS) is the most common reproductive endocrine disorder among women of reproductive age, which is one of the main causes of anovulatory infertility. Even though the rapidly developed assisted reproductive technology (ART) could effectively solve fertility problems, some PCOS patients still have not obtained satisfactory clinical outcomes. The poor quality of oocytes caused by the abnormal follicular development of PCOS may directly contribute to the failure of ART treatment. Ovarian granulosa cells (GCs) are the most closely related cells to oocytes, and changes in their functional status have a direct impact on oocyte formation. Previous studies have shown that changes in the ovarian microenvironment, like oxidative stress and inflammation, may cause PCOS-related aberrant follicular development by impairing the physiological state of the GCs. Therefore, optimizing the ovarian microenvironment is a feasible method for enhancing the development potential of PCOS oocytes. In this study, we first detected the expression of inflammatory-related factors (TGF-β1, IL-10, TNFα, IL-6) and oxidative stress-related factors (HIF-1α and VEGFA), as well as the proliferation ability and apoptosis level of GCs, which were collected from control patients (non-PCOS) and PCOS patients, respectively. Subsequently, human ovarian granulosa cell line (KGN) cells were used to verify the anti-inflammatory and anti-oxidative stress effects of chitosan oligosaccharide (COS) on GCs, as well as to investigate the optimal culture time and concentration of COS. The optimal culture conditions were then used to culture GCs from PCOS patients and control patients. The results showed that GCs from PCOS patients exhibited obvious inflammation and oxidative stress and significantly reduced proliferation and increased apoptosis. Furthermore, COS can increase the expression of anti-inflammatory factors (TGF-β1 and IL-10) and decrease the expression of pro-inflammatory factors (TNFα and IL-6), as well as promote the proliferation of GCs. Moreover, we found that COS can reduce the level of reactive oxygen species in GCs under oxidative stress by inhibiting the expression of HIF-1α and VEGFA and by suppressing the apoptosis of GCs induced by oxidative stress. We find that inflammation and oxidative stress exist in the GCs of PCOS patients, and COS can reduce these factors, thereby improving the function of GCs.


Ketamine as a rapid-acting agent for suicidal ideation: A meta-analysis.
The current systematic review and meta-analysis aimed at exploring acute effects of intravenous (IV) ketamine, an antagonist of N-methyl-D-aspartate (NMDA), in subjects with current suicidal ideation. We included clinical trials testing a single IV dose of ketamine and assessing changes in suicidal ideation within 4h after treatment. Meta-analyses based on random-effects models, were carried out generating pooled standardized mean differences (SMDs) between endpoint and baseline scores. Heterogeneity among studies was estimated using the I2 index. We searched main Electronic Databases, identifying five studies that met our inclusion criteria. The trials included 99 subjects treated with IV ketamine bolus or infusion. Data showed a large (SMD=-0.92; 95%CI: -1.40 to -0.44; p<0.001) and consistent (I2=21.6%) decrease of suicidal ideation, with effects comparable between IV bolus and infusion ketamine. Additional analyses confirmed the efficacy of ketamine across different time points. However, relevant, emerging evidence should be considered as 'very low' so far. Randomized, controlled and adequately powered trials are needed.


Toward a Trauma-Responsive Juvenile Justice System.
Childhood traumatic stress is predictive of delinquency in adolescence, the severity of delinquent offenses, and the likelihood of reoffending. Over the past decade, the Juvenile Justice Section of North Carolina's Department of Public Safety has advanced from trauma-informed toward trauma-responsive care. Efforts taken and lessons learned are presented.


Psychotropic Drug Prescription in Patients with Dementia: Nursing Home Residents Versus Patients Living at Home.
Psychotropic drugs are frequently prescribed in nursing homes (NH). Nonetheless, we hoped that institutionalization decreases the number of psychotropic drug classes prescribed, because NH residents may have more psychosocial interventions than patients living at home. The aim was to compare the type and number of psychotropic drugs prescribed in elderly NH residents with dementia with those in community-living patients. This cross-sectional study included elderly patients (at least 75 years old) with dementia recorded in the National Alzheimer's data Bank ("Banque Nationale Alzheimer") during the year 2012 and who were taking at least one psychotropic drug. Psychotropic drugs were classified as follows: antidepressant, anxiolytic, hypnotic, and antipsychotic drugs. Patients were classified into three categories of dementia severity according to the MMSE score. Among the 50,932 patients with dementia recorded in the BNA, 40.1% had at least one psychotropic drug prescribed. Most of the patients who were treated by at least one psychotropic drug class had antidepressant therapy (69.0%), whatever their residence type, and 16.1% were treated with antipsychotics. Among the study population, 51.9% of the NH residents and 67.4% of the patients living at home had only one psychotropic drug class prescribed. Living in a NH was significantly associated with the more frequent prescription of anxiolytic, hypnotic, and antipsychotic drugs, and with a greater number of psychotropic drug classes prescribed, whatever the severity of the dementia. We underlined the more frequent prescription of psychotropic drugs in NH residents regardless of MMSE scores.


Parameters of interferon action: I. Immunological effects of whole cell leukocyte interferon (IFN-alpha) in phase I-II trials.
The antitumor mechanisms of the interferons (IFN) have yet to be fully elucidated. Augmentation of natural killer (NK) cell activity in vitro and in vivo by IFN has regularly been assessed in clinical trials. We have measured NK activity against K562 target cells at various effector-to-target ratios, in patients receiving leukocyte IFN-alpha (HuLeIFN) in various schedules, as well as T-cell subsets determined by indirect immunofluorescence using Leu series monoclonal antibodies (Becton-Dickinson). The effect of HuLeIFN on the endocrine system has also been examined in selected trials. The preliminary results of these studies reveal that NK activity rose during the first 8 days of HuLeIFN therapy in patients with initially low levels of target cell lysis (less than 50% NK activity at either 50:1 or 25:1 ratios). Tachyphylaxis, with a decremental effect of HuLeIFN on NK activity, ensued during treatment, whether at the same or escalated doses. NK activity rose repeatedly during intermittent schedules of i.m. HuLeIFN given daily x 5 every 21 days with escalation cycles. A decreasing trend in the ratio of Leu 3a to Leu 2a (helper phenotype/suppressor phenotype) was also seen overall. Of the endocrine parameters evaluated, the only remarkable finding was an increase in serum cortisol level following ACTH stimulation following HuLeIFN. Intramuscular HuLeIFN has been shown to augment NK activity, to perturb the T-cell-lymphocyte balance, and to affect the pituitary-adrenal axis in vivo.


Evaluation of Upper Body and Lower Limbs Kinematics through an IMU-Based Medical System: A Comparative Study with the Optoelectronic System.
In recent years, the use of inertial-based systems has been applied to remote rehabilitation, opening new perspectives for outpatient assessment. In this study, we assessed the accuracy and the concurrent validity of the angular measurements provided by an inertial-based device for rehabilitation with respect to the state-of-the-art system for motion tracking. Data were simultaneously collected with the two systems across a set of exercises for trunk and lower limbs, performed by 21 healthy participants. Additionally, the sensitivity of the inertial measurement unit (IMU)-based system to its malpositioning was assessed. Root mean square error (RMSE) was used to explore the differences in the outputs of the two systems in terms of range of motion (ROM), and their agreement was assessed via Pearson's correlation coefficient (PCC) and Lin's concordance correlation coefficient (CCC). The results showed that the IMU-based system was able to assess upper-body and lower-limb kinematics with a mean error in general lower than 5° and that its measurements were moderately biased by its mispositioning. Although the system does not seem to be suitable for analysis requiring a high level of detail, the findings of this study support the application of the device in rehabilitation programs in unsupervised settings, providing reliable data to remotely monitor the progress of the rehabilitation pathway and change in patient's motor function.


Survival of a 300-g infant ventilated by high-frequency oscillatory ventilation for respiratory distress syndrome.
We report a case of an infant delivered before the completion of 26 wks' gestation, weighing 300 g at birth, and treated with high-frequency oscillatory ventilation for respiratory distress syndrome. Her neurologic examination at 18 months of age is compatible with mild delay in gross and fine motor skills.


Vitamin C: from popular food supplement to specific drug.
The daily requirement of a human person for vitamin C (ascorbic acid) has now been established at 100 mg. This value was already on the map when Arnold Durig put together the most important needs of nutritional ingredients. The modern value rests on the saturating level of ascorbate in leukocytes, which is in the millimolar range. The mechanism of accumulation of ascorbate in these cells rests on the uptake of oxidized dehydroascorbic acid. It is very efficient and avoids loss of vitamin which occurs in vitro when ascorbate is oxidized because of the great instability of the dehydro form. Therefore and increased requirement in case of infection is very unlikely from the biochemical point of view. However, low concentrations of ascorbate are found in patients suffering from arterial diseases or diseases accompanied by arterial damage such as diabetes mellitus. Ascorbate is known as a protection factor for the arterial endothel, but it is not clear by what mechanism this protection is brought about. Moreover, under clinical conditions very high concentrations are needed, which are achieved only by intravenous infusion, and the protection is only observed when the disease is manifest, not in healthy people. Therefore, also in this respect an increase in daily intake seems of no prophylactic value. Thus, by using high concentrations of ascorbate as an i.v. drug, effects of this substance frequently observed in vitro, could be used for therapy. This includes not only treatment of arterial diseases, but also relates to the cytotoxic effects of the vitamin against certain tumor cells and may assist conventional chemotherapy.


Hedgehog Signaling: From Basic Biology to Cancer Therapy.
The Hedgehog (HH) signaling pathway was discovered originally as a key pathway in embryonic patterning and development. Since its discovery, it has become increasingly clear that the HH pathway also plays important roles in a multitude of cancers. Therefore, HH signaling has emerged as a therapeutic target of interest for cancer therapy. In this review, we provide a brief overview of HH signaling and the key molecular players involved and offer an up-to-date summary of our current knowledge of endogenous and exogenous small molecules that modulate HH signaling. We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted.


Silica supported phosphomolybdic acid: an efficient heterogeneous catalyst for Friedlander synthesis of quinolines.
Silica supported phosphomolybdic acid, an eco-friendly heterogeneous catalyst, has been found to be highly efficient for Friedlander synthesis of quinolines in excellent yields. A variety of ketones afford the quinolines smoothly. The catalyst can be easily recovered and reused.


Electrical transport measured in atomic carbon chains.
The first electrical-transport measurements of monatomic carbon chains are reported in this study. The chains were obtained by unraveling carbon atoms from graphene ribbons while an electrical current flowed through the ribbon and, successively, through the chain. The formation of the chains was accompanied by a characteristic drop in the electrical conductivity. The conductivity of the chains was much lower than previously predicted for ideal chains. First-principles calculations using both density functional and many-body perturbation theory show that strain in the chains has an increasing effect on the conductivity as the length of the chains increases. Indeed, carbon chains are always under varying nonzero strain that transforms their atomic structure from the cumulene to the polyyne configuration, thus inducing a tunable band gap. The modified electronic structure and the characteristics of the contact to the graphitic periphery explain the low conductivity of the locally constrained carbon chain.


Does the Vascular Surgery Board of the American Board of Surgery work?
Recommendations to form an independent American Board of Vascular Surgery were made several years ago by leaders in vascular surgery. All major vascular societies in the United States voted by majority rule to approve the formation of this organization. Although the Vascular Surgery Board of the American Board of Surgery is well intentioned, its focus and intentions are outdated because it is subservient to the American Board of Surgery.


Inflammatory responses to Pneumocystis carinii in mice selectively depleted of helper T lymphocytes.
Pneumocystis carinii is the most important pulmonary pathogen in patients with the acquired immunodeficiency syndrome, but host defenses against P. carinii are not well characterized. We recently reported an experimental model of P. carinii infection, in which mice selectively depleted of CD4+ lymphocytes develop pulmonary infection after inoculation with P. carinii. In the current study, we compared lung inflammatory responses to P. carinii inoculation in CD4-depleted mice and in normal mice in order to further characterize host defenses against P. carinii. We hypothesized that depletion of CD4+ lymphocytes would prevent recruitment and activation of inflammatory cells in the lungs of these mice, allowing progressive infection with P. carinii. We found that CD4-depleted mice were unable to recruit CD4+ lymphocytes into their lungs and developed progressive infection with P. carinii, but mounted exuberant inflammatory responses to the organisms. These inflammatory responses were characterized by perivascular infiltration with mononuclear cells, increases in cell numbers in bronchoalveolar lavage (particularly CD8+ lymphocytes), and activation of alveolar macrophages (enhanced Ia antigen expression). In contrast, normal mice recruited CD4+ lymphocytes into their lungs and eliminated organisms with only minimal inflammatory responses. We conclude that depletion of CD4+ lymphocytes does not prevent the recruitment and activation of inflammatory cells in the lung. These inflammatory responses occur by mechanisms independent of CD4+ lymphocytes and are insufficient to provide effective host defense against P. carinii.


Red and blue light-specific metabolic changes in soybean seedlings.
Red and blue artificial light sources are commonly used as photosynthetic lighting in smart farm facilities, and they can affect the metabolisms of various primary and secondary metabolites. Although the soybean plant contains major flavonoids such as isoflavone and flavonol, using light factors to produce specific flavonoids from this plant remains difficult because the regulation of light-responded flavonoids is poorly understood. In this study, metabolic profiling of soybean seedlings in response to red and blue lights was evaluated, and the isoflavone-flavonol regulatory mechanism under different light irradiation periods was elucidated. Profiling of metabolites, including flavonoids, phenolic acids, amino acids, organic acids, free sugars, alcohol sugars, and sugar acids, revealed that specific flavonol, isoflavone, and phenolic acid showed irradiation time-dependent accumulation. Therefore, the metabolic gene expression level and accumulation of isoflavone and flavonol were further investigated. The light irradiation period regulated kaempferol glycoside, the predominant flavonol in soybeans, with longer light irradiation resulting in higher kaempferol glycoside content, regardless of photosynthetic lights. Notably, blue light stimulated kaempferol-3-O-(2,6-dirhamnosyl)-galactoside accumulation more than red light. Meanwhile, isoflavones were controlled differently based on isoflavone types. Malonyl daidzin and malonyl genistin, the predominant isoflavones in soybeans, were significantly increased by short-term red light irradiation (12 and 36 h) with higher expressions of flavonoid biosynthetic genes, which contributed to the increased total isoflavone level. Although most isoflavones increased in response to red and blue lights, daidzein increased in response only to red light. In addition, prolonged red light irradiation downregulated the accumulation of glycitin types, suggesting that isoflavone's structural specificity results in different accumulation in response to light. Overall, these findings suggest that the application of specific wavelength and irradiation periods of light factors enables the regulation and acquisition of specialized metabolites from soybean seedlings.


Intracellular β-nicotinamide adenine dinucleotide inhibits the skeletal muscle ClC-1 chloride channel.
ClC-1 is the dominant sarcolemmal chloride channel and plays an important role in regulating membrane excitability that is underscored by ClC-1 mutations in congenital myotonia. Here we show that the coenzyme β-nicotinamide adenine dinucleotide (NAD), an important metabolic regulator, robustly inhibits ClC-1 when included in the pipette solution in whole cell patch clamp experiments and when transiently applied to inside-out patches. The oxidized (NAD(+)) form of the coenzyme was more efficacious than the reduced (NADH) form, and inhibition by both was greatly enhanced by acidification. Molecular modeling, based on the structural coordinates of the homologous ClC-5 and CmClC proteins and in silico docking, suggest that NAD(+) binds with the adenine base deep in a cleft formed by ClC-1 intracellular cystathionine β-synthase domains, and the nicotinamide base interacts with the membrane-embedded channel domain. Consistent with predictions from the models, mutation of residues in cystathionine β-synthase and channel domains either attenuated (G200R, T636A, H847A) or abrogated (L848A) the effect of NAD(+). In addition, the myotonic mutations G200R and Y261C abolished potentiation of NAD(+) inhibition at low pH. Our results identify a new biological role for NAD and suggest that the main physiological relevance may be the exquisite sensitivity to intracellular pH that NAD(+) inhibition imparts to ClC-1 gating. These findings are consistent with the reduction of sarcolemmal chloride conductance that occurs upon acidification of skeletal muscle and suggest a previously unexplored mechanism in the pathophysiology of myotonia.


ATP11C mutation is responsible for the defect in phosphatidylserine uptake in UPS-1 cells.
Type IV P-type ATPases (P4-ATPases) translocate phospholipids from the exoplasmic to the cytoplasmic leaflets of cellular membranes. We and others previously showed that ATP11C, a member of the P4-ATPases, translocates phosphatidylserine (PS) at the plasma membrane. Twenty years ago, the UPS-1 (uptake of fluorescent PS analogs) cell line was isolated from mutagenized Chinese hamster ovary (CHO)-K1 cells with a defect in nonendocytic uptake of nitrobenzoxadiazole PS. Due to its defect in PS uptake, the UPS-1 cell line has been used in an assay for PS-flipping activity; however, the gene(s) responsible for the defect have not been identified to date. Here, we found that the mRNA level of ATP11C was dramatically reduced in UPS-1 cells relative to parental CHO-K1 cells. By contrast, the level of ATP11A, another PS-flipping P4-ATPase at the plasma membrane, or CDC50A, which is essential for delivery of most P4-ATPases to the plasma membrane, was not affected in UPS-1 cells. Importantly, we identified a nonsense mutation in the ATP11C gene in UPS-1 cells, indicating that the intact ATP11C protein is not expressed. Moreover, exogenous expression of ATP11C can restore PS uptake in UPS-1 cells. These results indicate that lack of the functional ATP11C protein is responsible for the defect in PS uptake in UPS-1 cells and ATP11C is crucial for PS flipping in CHO-K1 cells.


An analysis of policy success and failure in formal evaluations of Australia's national mental health strategy (1992-2012).
Heightened fiscal constraints, increases in the chronic disease burden and in consumer expectations are among several factors contributing to the global interest in evidence-informed health policy. The present article builds on previous work that explored how the Australian Federal Government applied five instruments of policy, or policy levers, to implement a series of reforms under the Australian National Mental Health Strategy (NMHS). The present article draws on theoretical insights from political science to analyse the relative successes and failures of these levers, as portrayed in formal government evaluations of the NMHS. Documentary analysis of six evaluation documents corresponding to three National Mental Health Plans was undertaken. Both the content and approach of these government-funded, independently conducted evaluations were appraised. An overall improvement was apparent in the development and application of policy levers over time. However, this finding should be interpreted with caution due to variations in evaluation approach according to Plan and policy lever. Tabulated summaries of the success and failure of each policy initiative, ordered by lever type, are provided to establish a resource that could be consulted for future policy-making. This analysis highlights the complexities of health service reform and underscores the limitations of narrowly focused empirical approaches. A theoretical framework is provided that could inform the evaluation and targeted selection of appropriate policy levers in mental health.


Hypertension in early alcohol withdrawal in chronic alcoholics.
Hypertension is an established risk factor in chronic alcoholics, but little is known about the relationship between blood pressure (BP), severity of their alcohol abuse, and severity of alcohol withdrawal syndrome (AWS). BP was assessed daily for 18 days in a series of chronic alcoholics on early alcohol withdrawal (AW), while also assessing the severity of their AWS on the CIWA-Ar scale. A sharp and sustained decrease in BP was observed after AW; at T0, BP had increased in 55% of patients, and at T18 in 21%. The variation of BP is partially explained by years of at-risk drinking and AWS severity, but other factors may play a role in hypertension in alcoholics, as a large amount of BP variation was not explained by the alcohol-abuse-related parameters that we studied. BP values were not correlated with cigarette smoking, anxiety, or depression. Hypertension found in 'detoxified' alcoholics (approximately 20%) may be related to alcohol-independent hypertension or to a long-lasting alcohol-induced derangement of the BP regulating mechanisms. Further research is needed in these patients to elucidate the mechanisms of persistent hypertension and to set up a treatment protocol. At present, careful monitoring is advisable, as well as pharmacological treatment for moderate or severe hypertension; often a modification of life-style is needed which includes physical activity and possibly sodium (Na) restriction, since hypertension in detoxified alcoholics seems to be Na sensitive. Complete alcohol abstinence must be recommended to all hypertensive alcoholics, as AW-induced transient hypertension was found to be harmless in all our subjects, and abstinence leads to a complete recovery from hypertension in most cases.


Mechanical ventilation practice in Egyptian pediatric intensive care units.
Mechanical ventilation is one of the indispensable tools in pediatric intensive care units. Few studies addressed the epidemiology of pediatric patients on mechanical ventilation and the frequently used modes of ventilation. This is the first study to describe the practice of mechanical ventilation (MV) in Egyptian pediatric intensive care units (PICUs). This prospective observational study was conducted from January 2014 to December 2014 in two pediatric intensive care units at Cairo University Pediatric Hospital. The study included all children who were intubated and mechanically ventilated for more than 12 hours of admission. Pre-coded data was entered into the SPSS version 21 for data analysis. Comparison between groups was performed using Mann Whitney test for quantitative variables and Chi square with Fisher's exact test for qualitative ones. Multivariate logistic regression model was conducted to explore the significant predictors for PICU mortality. In total, 893 children were admitted and 293 were mechanically ventilated. The incidence of utilizing MV in children was 32.8%. Neurologic causes were the most common reasons for initiation of MV, with 114 (38.9%) cases. The most commonly preferred mode for initiation of MV is SIMV with PS. Complication occurred in 117 (39.9%) of the cases. The most commonly preferred method of weaning was PS with CPAP in 115/154 (74.7%) cases. Mortality occurred in 134/293 (45.7%) of patients. Duration of mechanical ventilation was significantly longer with neuromuscular diseases, and with the occurrence of complications (p<0.001). There was a significant relationship between mortality and higher PRISM III score, cardiovascular cases, sepsis, multiple organ dysfunction syndrome (MODS), ventilator-associated pneumonia (VAP), and with barotrauma. In our practice, MV is used oftentimes with almost a third of admissions requiring intubation for different reasons. Most children are ventilated due to neurologic causes. This study paves the way for improving our knowledge of MV with avoiding the fatal complications.


Demographic and cardiovascular risk factors associated with pre-frailty and frailty among community-dwelling older adults in Jakarta, Indonesia: Active Aging Study.
This study aimed to evaluate the prevalence of frailty and its determinants, especially in relation to chronic disease and lifestyle among elderly individuals. A cross-sectional study was conducted among 278 individuals aged 60 years and over living in Jakarta. All participants underwent assessment, including medical history-taking, physical examination and blood tests for the sugar level and lipid profile. Frailty was assessed using the Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe. All data were analysed using the chi-square test and multinomial logistic regression analysis. The prevalence of pre-frailty and frailty among the older adults was 40.6% and 28.8%, respectively. Female sex, lack of exercise, presence of cardiovascular diseases and high low-density lipoprotein cholesterol (LDL-C) level were associated with pre-frailty and frailty. Education for <9 years was associated only with frailty. After adjustments for all covariates, female sex (adjusted odds ratio [AOR] = 1.96, 95% confidence interval [CI]=1.07-3.60; AOR=3.93, 95% CI=1.87-8.24), lack of exercise (AOR=l4.81, 95% CI=5.07-43.26; AOR=49.48, 95% CI=16.20-151.09) and presence of cardiovascular diseases (AOR=5.32, 95% CI= 1.40-19.20; AOR=6.06, 95% CI= 1.63-22.56) were associated with pre-frailty and frailty. Meanwhile, education for <9 years (AO R= 1.97, 95% CI=1.05-3.69) and high LDL-C level (AOR=3.52, 95% CI=1.14-10.88) were associated with frailty. Exercise, early screening and intervention for cardiovascular diseases and maintenance of lower LDL-C levels may prevent and slow the progression of frailty.


Carcinoid syndrome: its relevance to the anaesthetist.
This paper presents the pathology, pharmacophysiology and therapy of the carcinoid syndrome. Forty reports from the literature are reviewed and the anaesthetic management of the patients is discussed. The carcinoid syndrome is a rare multihumoral endocrine disease. Secretions may be stimulated by certain anaesthetic and surgical manoeuvres and produce undesirable, and occasionally fatal, cardiovascular and respiratory complications. A radical surgical approach to the disease is current. Anaesthetists may therefore be involved in the management of these patients more frequently than before. The implication of both serotonin and bradykinin in the pharmacophysiology of this disease allows a more rational approach to the treatment of complications occurring during anaesthesia. However, other, as yet undiscovered vasoactive substances, may be involved.


A prospective randomized study: day 2 versus day 5 embryo transfer.
This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.


Image-Guided Access for Percutaneous Nephrolithotomy: A Single-Center Experience in 591 Patients.
We present our experience in image-guided percutaneous nephrolithotomy (PCNL) access in 591 patients. An IRB-approved review of all adult PCNL cases from 2009 to 2014 was performed. Patient data, information regarding stone size and location, procedural details, clinical success, complications by access site (upper pole versus middle or lower pole) and puncture location (supracostal versus infracostal) were recorded. In this study, 591 patients (314 males, 278 females, mean stone size: 23 mm, range: 4-100 mm) were included. Stone clearance was achieved in 66% of patients. There were 174 total complications (29.3%). Upper pole access was less likely to require a secondary access to achieve stone clearance (p = 0.02) and was preferentially used for both larger stones (p = 0.006) and staghorn calculi (p = 0.001). If a supracostal approach to the upper pole was used, there were significantly more complications compared to an infracostal approach (p = 0.002). Upper pole access for PCNL provides anatomic advantages for stone clearance but significantly increases the risk for complications when a supracostal puncture is required.


Non-specific analgesia during a clinical trial in fibromyalgia.
When patients suffering from fibromyalgia undergo a therapeutic trial, a non-negligible part of analgesia is not explained by the drug itself. The mechanisms of this non-specific effect need to be understood. We undertook secondary analyses of a double-blind randomized trial in fibromyalgia patients in which 100 mg/day milnacipran was not found superior to placebo. Data from 49 patients belonging to both groups were pooled. Both before treatment and one month after treatment, all patients underwent a CaNTAB® neuropsychological test (related to spatial planning, reaction time, decision-making and risk-taking, and ability to name objects), and measurements of sensation and pain thresholds to heat and cold, supraliminal heat pain threshold, punctuate mechanical pain threshold and temporal summation, mechanical allodynia to skin brushing, and response to conditioned pain modulation. We studied the baseline predictors of analgesia and the indicators of change associated to analgesia separately. A stepwise approach was used to select the factors to enter into the final ANCOVAs, in which age, body mass index, treatment group and pain at baseline were covariates. No baseline predictor of non-specific analgesia other than pain at baseline was found to be predictive. Conversely, several neuropsychological (higher performance) or psychophysical (lower sensitivity) changes correlated with analgesia in unadjusted analyses. Multivariable analyses identified increases in warm/heat thermal thresholds and an increased ability to name objects, as factors associated with analgesia. The changes observed concomitantly to non-specific pain analgesia might be related to mild changes in brain functioning, based on convergent literature data.


[Effects of rice-duck farming system on biotic populations in paddy field].
A field experiment was conducted to study the effects of rice-duck farming on the related biotic populations in paddy field. The results showed that rice-duck farming had greater effects on the occurrence and damage of pests, pathogens and weeds, as well as the amount of pests' natural enemies in paddy field. The population of rice planthopper and leafhopper decreased by 64.8% and 78.5% after 12 and 42 days of duck-release, and the weeds decreased by 67.7% and 98.1% after 15 and 45 days of duck-release, respectively, compared with the control. The sheath blight index at the maximum tillering stage and full-heading stage in the rice-duck plots were 40.4% and 62.0% lower than those in the control plot, respectively. The population of spiders in duck-released field was increased obviously, which in turn decreased the damage of rice pests.


Insulin resistance is associated with hirsutism in unselected reproductive-aged women.
Hirsutism affects 5%-10% of reproductive-aged women worldwide and exhibits clinical importance as a cutaneous manifestation of underlying hyperandrogenism. Racial and genetic factors play roles in manifestation of hirsutism, and the prevalence of hirsutism seems to be low in East Asians. However, the reference value of the modified Ferriman-Gallwey (mFG) score to diagnose hirsutism and the prevalence of hirsutism have not been determined in Korean populations to date. We aimed to investigate the distribution of the mFG score and establish its reference value for defining hirsutism and to examine its relationship with metabolic and reproductive traits in reproductive-aged Korean women. We enrolled 2139 female volunteers of reproductive age (15-39 years). We recorded mFG scores from 0 to 4 on 9 different body locations (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back and thighs). Hirsutism was defined as >95th percentile of mFG score. In addition, a 75-g oral glucose tolerance test was performed, and the homoeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The mFG values of the 50th, 75th, 90th and 95th percentiles were 0, 1, 4 and 6, respectively. Therefore, the mFG score was indicative of hirsutism when the score was 6 or greater, which represents the 95th percentile. In the correlation analysis, total testosterone, free testosterone, fasting plasma insulin and HOMA-IR were positively correlated with mFG score (all Ps <0.05). Multiple linear regression analysis revealed that HOMA-IR (β = 0.081) was positively associated with mFG score after adjustments for age, body mass index, total testosterone and the number of menses per year (P < 0.001). In conclusion, setting the 95th percentile of the mFG score as normal, the reference value to define hirsutism was 6 in reproductive-aged Korean women. HOMA-IR was positively associated with the mFG score even after adjustment for biochemical hyperandrogenism.


Imaging features of Paget's disease on 11C choline PET/CT.
The purpose of this study was to investigate the appearance of Paget's disease (PD) on 11C choline PET/CT and correlate these findings to serum alkaline phosphatase (ALP) level and skeletal scintigraphy. With IRB approval, our institutional 11C choline PET/CT database (9/2005-6/2015) was searched for patients with PD. Site of osseous involvement, CT appearance, and multiple semi-quantitative measures were measured and correlated with ALP and degree of uptake on bone scan. Our search identified 10 males (mean age 79.6 ± 7.8 years). Four had polyostotic disease and seven had more than one 11C choline PET/CT. In total, 58 affected bones were evaluated on 25 PET/CTs. Mean lesion SUVmax was 2.6 ± 0.89 (range 1.0-4.4), SUVmax/Liver SUVmean 0.33 ± 0.13 (0.12-0.61), SUVmax/Liver SUVmax 0.29 ± 0.11 (0.10-0.52), SUVmax/BP SUVmean 2.47 ± 0.86 (0.91-4.22), and SUVmax/BP SUVmax 1.92 ± 0.71 (0.68-3.45). There was no correlation between ALP and any semiquantitative measure. Bone scan uptake was marked in 41 bones, moderate in nine, and mild in six. There was no correlation between lesion SUVmax and bone scan uptake (P = 0.26). Paget's disease on 11C choline PET/CT demonstrates mild to moderate activity, which does not correlate with bone scan uptake or ALP level. It is important to recognize Paget's disease as a potential pitfall on 11C choline PET/CT. However, the characteristic appearance on the CT portion of PET/CT examinations should allow confident diagnosis and differentiation from prostate cancer osseous metastases.


Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma--a study of 51 cases from a low-endemicity area.
A total of 51 cases (19 males and 32 females) of intrahepatic cholangiocellular carcinoma (CCC) from a low-endemicity area of primary liver cancer was analyzed during the periods from 1958 to 1979 and from 1984 to 1991. The mean annual age-adjusted incidence rate was 0.44 for males and 0.56 for females per 100,000 inhabitants. CCC was diagnosed before death in only 31%. There was a female predominance in patients over 70 years of age (p < 0.05). At presentation, malaise (85%), weight loss (73%) abdominal pain (50%) and hepatomegaly (80%) were common. The median survival time from diagnosis was 2 months. The mean age at the time of death was 72 years (range 41-92). At autopsy, cholelithiasis was found in 61% (81% in patients older than 70 years) and cirrhosis in 30% of patients. Cholelithiasis was more common in CCC (p < 0.01) than in hepatocellular carcinoma cases with the same mean age. Not one case of inflammatory bowel disease was found. The gross appearance of the tumor was predominantly massive (49%) or multinodular (35%). The most common histological features were tubular pattern of growth (82%) and abundant fibrous stroma. Metastases were particularly associated with the lymph nodes (41%), skeleton (26%) and lungs (16%).


Dissection of specific binding of HIV-1 Gag to the 'packaging signal' in viral RNA.
Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the 'packaging signal' (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding of recombinant HIV-1 Gag protein to Cy5-tagged 190-base RNAs. At physiological ionic strength, Gag binds with very similar, nanomolar affinities to both Ψ-containing and control RNAs. We challenged these interactions by adding excess competing tRNA; introducing mutations in Gag; or raising the ionic strength. These modifications all revealed high specificity for Ψ. This specificity is evidently obscured in physiological salt by non-specific, predominantly electrostatic interactions. This nonspecific activity was attenuated by mutations in the MA, CA, and NC domains, including CA mutations disrupting Gag-Gag interaction. We propose that gRNA is selectively packaged because binding to Ψ nucleates virion assembly with particular efficiency.


Dewetting at soft viscoelastic interfaces.
The dewetting transition of thin liquid films (approximately 100 nm) at soft viscoelastic interfaces is analyzed theoretically. It is shown that viscoelastic losses in the soft material can drastically increase the time to complete the dewetting. Thus, the influence of the thinning of the liquid film, due to the hydrodynamic drainage caused by the external applied pressure, has to be considered too. The squeezing pressure coupled with the hydrodynamic drainage may slow down the dewetting to almost zero growth rate of the dry zone; in this case a trapped rim of fluid should be observed.


The Complete Genome Sequence of Adansonia digitata (Malvaceae, Malvales), the African Baobab.
Adansonia digitata, the African Baobab, is a long-lived tree species found in sub-Saharan Africa. We present the whole genome sequence of this species. Illumina paired-end reads were assembled by a de novo method followed by a finishing step. The raw and assembled data are publicly available via GenBank: Sequence Read Archive (SRR23340274) and assembled genome (JAQSVH000000000).


Noniterative algorithm for improving the accuracy of a multicolor-light-emitting-diode-based colorimeter.
We present a noniterative algorithm to reliably reconstruct the spectral reflectance from discrete reflectance values measured by using multicolor light emitting diodes (LEDs) as probing light sources. The proposed algorithm estimates the spectral reflectance by a linear combination of product functions of the detector's responsivity function and the LEDs' line-shape functions. After introducing suitable correction, the resulting spectral reflectance was found to be free from the spectral-broadening effect due to the finite bandwidth of LED. We analyzed the data for a real sample and found that spectral reflectance with enhanced resolution gives a more accurate prediction in the color measurement.


A zebrafish model to study small-fiber neuropathy reveals a potential role for GDAP1.
Mutations in genes involved in mitochondrial dynamics (fusion and fission) have been implicated in many peripheral neuropathies. We hypothesized that defects in these genes could result in a phenotype resembling features of small-fiber neuropathy (SFN). This was investigated in zebrafish by knocking down two genes involved in mitochondrial dynamics gdap1 (possibly fission and motility) and opa1 (fusion) using established morpholinos. Our read-outs were nerve density in the caudal fin and a behavioral response to temperature changes, both based on comparable hallmarks of SFN in patients. Knockdown of gdap1 resulted in zebrafish embryos with a reduced density of sensory neurites compared to control morpholino-injected embryos. Furthermore, these embryos demonstrated a decreased temperature-related activity. In contrast, a knockdown of opa1 did not affect the density of sensory neurites nor the temperature-related activity. However, only the opa1 morphants had an effect on mitochondrial network morphology. As we were not able to visualize the mitochondria in the neurons, it could well be that changes in the mitochondrial network remained undetected. Our data indicate that GDAP1 knockdown affects sensory neurite development, however, it is unclear if a problem in mitochondrial fission and network formation is the pathophysiological mechanism. Although we did not observe an effect of inhibiting mitochondrial fusion during development, we still propose that genes involved in mitochondrial dynamics should be screened for mutations in patients with SFN.


Geotextile composition, application and ecotoxicology-A review.
Geosynthetics is the umbrella term for thin, flexible material sheets applied in civil and environmental engineering, of which geotextiles form the largest group. Most geotextiles consist of a polymer from the polyolefin, polyester or polyamide family, and additives to improve their stability. The polymer may degrade into microplastic particles over time and under various conditions and can cause adverse effects, as species may ingest these particles or encounter adverse effects due to the interference of the particles with e.g. their photosynthesis system in the case of algae. Leaching of additives may occur from the intact material, as they are often not covalently bound to the polymer backbone, but is greatly enhanced when micro-sized plastic particles have been formed. A total of 42 polymer additives were identified, of which 26 had ecotoxicity information available in terms of a REACH persistence, toxicity and bioaccumulation (PBT) assessment. Of these, 15 were classified as (very) persistent and 2 as toxic. A survey to assess potential toxicity of the remaining 16 substances revealed that no ecotoxicity studies had been performed on 13 of these compounds. For 3 compounds, other toxicity data was found, as well as of several chemical groups known to be used as additives in geotextiles. The current knowledge is thus lacking in two domains: on the one hand, ecotoxicity data is scarce as many substances have not yet been the subject of ecotoxicological studies. On the other hand, in situ toxic effects might be missed by the current approach of single compound toxicity testing. Moreover, environmental occurrence data of the additives are extremely scarce.


Density and birefringence of a highly stable α,α,β-trisnaphthylbenzene glass.
Spectroscopic ellipsometry has been used to understand the properties of α,α,β-trisnaphthylbenzene (ααβ-TNB) glasses vapor-deposited at a substrate temperature of 295 K (0.85 T(g)). In a single temperature ramping experiment, a range of properties of the as-deposited glass can be measured, including density, fictive temperature, onset temperature, thermal expansion coefficient, and birefringence. The vapor-deposited ααβ-TNB glass is 1.3% more dense than the ordinary glass prepared by cooling at 1 K/min, is found to be birefringent, has a fictive temperature 35 K below that of the ordinary glass, and an onset temperature 20 K above that of the ordinary glass. The thermal expansion coefficient of the vapor-deposited ααβ-TNB glass is 14% lower than that of the ordinary glass, indicating that lower portions of the potential energy landscape have more harmonic potential minima than the parts accessible to the ordinary glass.


[Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities].
Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism.


A Thermal Model for Carbon Nanotube Interconnects.
In this work, we have studied Joule heating in carbon nanotube based very large scale integration (VLSI) interconnects and incorporated Joule heating influenced scattering in our previously developed current transport model. The theoretical model explains breakdown in carbon nanotube resistance which limits the current density. We have also studied scattering parameters of carbon nanotube (CNT) interconnects and compared with the earlier work. For 1 µm length single-wall carbon nanotube, 3 dB frequency in S12 parameter reduces to ~120 GHz from 1 THz considering Joule heating. It has been found that bias voltage has little effect on scattering parameters, while length has very strong effect on scattering parameters.


The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients.
To investigate the importance of age and other variables on the prevalence of secondary forms of hypertension in a hypertension referral center. Over the past 18 years 4429 patients have been referred by their physicians for a 1-day blood pressure study to investigate secondary causes of hypertension. The 1-day blood pressure study included a history and physical examination by a physician, and measurements of serum sodium, potassium, creatinine, thyroxine, thyroid stimulating hormone, stimulated plasma renin activity, blood pressure response to the angiotensin II analogue saralasin, recumbent and upright plasma catecholamines, and plasma cortisol and aldosterone after infusion of 2 liters 0.9% saline over 3-4 h. The prevalence of secondary forms of hypertension was 10.2%, including renovascular hypertension (3.1%), primary aldosteronism (1.4%), Cushing's syndrome (0.5%), pheochromocytoma (0.3%), primary hypothyroidism (3.0%) and a serum creatinine > 2.0 mg/dl (1.8%). There was a very significantly increased prevalence with age of secondary forms of hypertension associated with renovascular hypertension, primary hypothyroidism and renal insufficiency. The concomitant presence of atherosclerosis significantly increased the prevalence of renovascular hypertension (9.5%) and renal insufficiency (8.0%). Increasing age and coexisting atherosclerosis have significant effects on the prevalence of secondary forms of hypertension.


Temporal encoding strategies result in boosts to final free recall performance comparable to spatial ones.
The method of loci is a highly effective mnemonic that recruits existing salient memory for spatial locations and uses the information as a scaffold for remembering a list of items (Yates, 1966). One possible account for the effectiveness of the spatial method of loci comes from the perspective that it utilizes evolutionarily preserved mechanisms for spatial navigation within the hippocampus (Maguire et al. in Proceedings of the National Academy of Sciences, 97(8), 4398-4403, 2000; O'Keefe & Nadel, 1978; Rodriguez et al. in Brain Research Bulletin, 57(3), 499-503, 2002). Recently, though, neurons representing temporal information have also been described within the hippocampus (Eichenbaum in Nature Reviews Neuroscience, 15(11), 732-744, 2014; Itskov, Curto, Pastalkova, & Buzsáki in The Journal of Neuroscience, 31(8), 2828-2834, 2011; MacDonald, Lepage, Eden, & Eichenbaum in Neuron, 71(4), 737-749, 2011; Mankin et al. in Proceedings of the National Academy of Sciences, 109(47), 19462-19467, 2012; Meck, Church, & Matell in Behavioral Neuroscience, 127(5), 642, 2013), challenging the primacy of spatial-based functions to hippocampal processing. Given the presence of both spatial and temporal coding mechanisms within the hippocampus, we predicted that primarily temporal encoding strategies might also enhance memory. In two different experiments, we asked participants to learn lists of unrelated nouns using the (spatial) method of loci (i.e., the layout of their home as the organizing feature) or using two novel temporal methods (i.e., autobiographical memories or using the steps to making a sandwich). Participants' final free recall performance showed comparable boosts to the method of loci for both temporal encoding strategies, with all three scaffolding approaches demonstrating performance well above uninstructed free recall. Our findings suggest that primarily temporal representations can be used effectively to boost memory performance, comparable to spatial methods, with some caveats related to the relative ease with which participants appear to master the spatial versus temporal methods.


Transient response of the time-delay system excited by Gaussian noise based on complex fractional moments.
In this paper, the transient response of the time-delay system under additive and multiplicative Gaussian white noise is investigated. Based on the approximate transformation method, we convert the time-delay system into an equivalent system without time delay. The one-dimensional Ito stochastic differential equation with respect to the amplitude response is derived by the stochastic averaging method, and Mellin transformation is utilized to transform the related Fokker-Planck-Kolmogorov equation in the real numbers field into a first-order ordinary differential equation (ODE) of complex fractional moments (CFM) in the complex number field. By solving the ODE of CFM, the transient probability density function can be constructed. Numerical methods are used to ascertain the effectiveness of the CFM method, the effects of system parameters on system response and the level of error vary with time as well as noise intensity are investigated. In addition, the CFM method is first implemented to analyze transient bifurcation, and the relation between CFM and bifurcation is discussed for the first time. Furthermore, the imperfect symmetry property appear on the projection map of joint probability density function.


Selective blockade of axonogenesis in cultured hippocampal neurons by the tyrosine phosphatase inhibitor orthovanadate.
Protein tyrosine phosphorylation has been implicated in several aspects of neurite outgrowth regulation. To address specific roles in early neuronal morphogenesis, hippocampal neurons in culture were treated with the tyrosine phosphatase inhibitor orthovanadate. This treatment completely suppressed axon formation, yet enhanced formation of minor neurites. The inhibition of axonogenesis was dose dependent and occurred in parallel with a marked increase in cellular phosphotyrosine immunoreactivity, which was especially concentrated within neuritic growth cones and showed partial colocalization with f-actin. Both the blockade of axonogenesis and the elevation of phosphotyrosine were completely reversible. An additional and unexpected effect of orthovanadate was the appearance of many binucleate neurons. Immunoblotting experiments using a phosphotyrosine-specific antibody revealed an orthovanadate-induced reversible hyperphosphorylation of several protein bands, especially of two at 115 and 125 kD. These data suggest a potentially important role for tyrosine phosphatases and their phosphoprotein substrates in axonogenesis.


Electrochemical biosensing with nanoparticles.
This minireview looks at the latest trends in the use of nanoparticles (NPs) in electrochemical biosensing systems. It includes electrochemical characterization of NPs for use as labels in affinity biosensors and other applications. DNA analysis involving NPs is one of the most important topics of current research in bionanotechnology. The advantages of the use of NPs in designing novel electrochemical sensors for DNA analysis are reviewed. Electrochemical NPs can also be used in designing immunoassays, offering the possibility of easy, low cost and simultaneous detection of several proteins. Research into NP applications in electrochemical analysis is in its infancy. Several aspects related to sensitivity as well integration of all the assay steps into a single one need to be improved.


Haemostatic activity of butanolic extracts of Lamium album and Lamium purpureum aerial parts.
Lamium album and Lamium purpureum are species belonging to the genus Lamium. Aerial parts of the two species and roots of Lamium album have applications in human and veterinary traditional medicine. Haemostatic properties of butanolic extracts of Lamium species were investigated by two experimental models in Wistar rats: haemostatic test by tail bleeding time determination and acenocoumarolcarrageenan test. Results of the haemostatic test by tail bleeding determination demonstrated haemostatic activity of both extracts. In the acenocoumarol-carrageenan test, only the Lamium album extract showed haemostatic activity, comparable to that of vitamin K. Based on the qualitative chemical data on iridoid glycosides (HPTLC), 8-acetylshanzhiside methyl ester might be assumed to be responsible for haemostatic activity. Based on the acute toxicity test, none of the extracts showed toxicity.


Plasma membrane Ca2+ transport: antagonism by several potential inhibitors.
Inside-out vesicles prepared from human red blood cells took up Ca2+ by an active transport process. Membranes from the same red blood cells displayed Ca2+-activated, Mg2+-dependent adenosine triphosphatase activity. Both the initial rate of Ca2+ transport and the (Ca2+ + Mg2+)-adenosine triphosphatase activity were increased approximately twofold by the calcium binding protein, calmodulin. Activities in the absence of added calmodulin were termed basal activities. Calmodulin-activated Ca2+ transport and adenosine triphosphatase activities could be antagonized in a relatively selective fashion by the phenothiazine tranquilizer drug, trifluoperazine. High concentrations of trifluoperazine also inhibited basal Ca2+ transport and adenosine triphosphatase activity. By contrast, calmodulin binding protein from beef brain selectively antagonized the effect of calmodulin on Ca2+ transport with no inhibition of basal activity. Ruthenium red antagonized calmodulin-activated and basal activity with equal potency. The results demonstrate that although phenothiazines can act as relatively selective antagonists of calmodulin-induced effects, other effects are possible and cannot be ignored. Calmodulin-binding protein may be a useful tool in the analysis of calmodulin functions. Ruthenium red probably interacts with Ca2+ pump adenosine triphosphatase at a site not related to calmodulin.


Efficacy of Sequential Therapy as the First-Line Treatment in the Eradication of Helicobacter pylori.
The Helicobacter pylori infection is a significant issue in global health as it is associated with a range of gastrointestinal disorders and an elevated likelihood of developing stomach cancer. The declining efficacy of standard triple therapy (TT) as the recommended treatment can be attributed to the emergence of drug-resistant strains. Sequential therapy (ST) has been recognized as an alternative approach, wherein a combination of proton-pump inhibitor (PPI) and amoxicillin is administered for the initial five days, followed by a combination of PPI, clarithromycin, and metronidazole for the subsequent five days. In this comprehensive systematic review and meta-analysis, we have thoroughly assessed the effectiveness and tolerability of ST as a primary treatment option in comparison to TT for the eradication of H. pylori. The analysis comprised a total of 15 randomized controlled trials, encompassing a sample size of 5,219 patients. The collective findings indicate that ST exhibits promise as it achieves higher rates of eradication. Additionally, it is worth noting that this approach has the potential to yield cost savings and enhance treatment compliance when compared to TT. To summarize, this systematic review and meta-analysis provide evidence that ST is a viable option for the initial treatment of H. pylori eradication. It shows potential benefits compared to the standard TT, especially when there is resistance to clarithromycin. In order to establish ST as the preferred first-line treatment, it is imperative that additional research be conducted to address the aforementioned limitations and thoroughly investigate its long-term efficacy and safety profiles. Nevertheless, it is required that additional research be conducted in order to adequately tackle the constraints of the current studies and solidify its position as a favored treatment alternative. It is also essential to consider ST as a viable approach to improve the rates of H. pylori eradication. This method should be thoroughly examined in clinical practice to gain a deeper understanding of its effectiveness.


Synthesis and upconversion luminescence of NaYF4:Yb3+,Tm3+/TiO2 nanocrystal colloidal solution.
NaYF4:Yb3+,Tm3+ upconversion nanocrystals were synthesized with oleic acid as a capping ligand. The as-prepared samples were redispersed in cyclohexane, forming transparent and stable solutions which perform bright blue upconversion. Inducing TiO2 as the outer layer of the fluoride cores, we investigated the effect of TiO2 on the upconversion process. The transmission electron microscopy (TEM) analysis indicated that titania successfully formed a coating layer on the surface of NaYF4:Yb3+, Tm3+ nanoparticles, and the average diameters of the NaYF4:Yb3+,Tm3+ nanocrystals and the NaYF4:Yb3+, Tm3+/TiO2 nanoparticles are about 14 and 40 nm, respectively. Under the excitation of a 980 nm laser, NaYF4:Yb3+, Tm3+ nanocrystals and TiO2-coated NaYF4:Yb3+, Tm3 core/shell structure sample exhibited distinct upconversion luminescent properties.


Synthesis of beta-nitrophenyl 2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl-D-glactopyranosides.
Reaction of 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide with p-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-alpha-D-galactopyranoside under the usual conditions, followed by removal of the p-methoxybenzylidene group and O-deacylation, gave crystalline p-nitrophenyl 2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl-alpha-D-galactopyranoside. The synthesis of p-nitrophenyl 2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl-beta-D-galactopyranoside has also been accomplished by a similar reaction-sequence.


Oxygen-Purged Microfluidic Device to Enhance Cell Viability in Photopolymerized PEG Hydrogel Microparticles.
Encapsulating cells within biocompatible materials is a widely used strategy for cell delivery and tissue engineering. While cells are commonly suspended within bulk hydrogel-forming solutions during gelation, substantial interest in the microfluidic fabrication of miniaturized cell encapsulation vehicles has more recently emerged. Here, we utilize multiphase microfluidics to encapsulate cells within photopolymerized picoliter-volume water-in-oil droplets at high production rates. The photoinitiated polymerization of polyethylene glycol diacrylate (PEGDA) is used to continuously produce solid particles from aqueous liquid drops containing cells and hydrogel forming solution. It is well understood that this photoinitiated addition reaction is inhibited by oxygen. In contrast to bulk polymerization in which ambient oxygen is rapidly and harmlessly consumed, allowing the polymerization reaction to proceed, photopolymerization within air permeable polydimethylsiloxane (PDMS) microfluidic devices allows oxygen to be replenished by diffusion as it is depleted. This sustained presence of oxygen and the consequential accumulation of peroxy radicals produce a dramatic effect upon both droplet polymerization and post-encapsulation cell viability. In this work we employ a nitrogen microjacketed microfluidic device to purge oxygen from flowing fluids during photopolymerization. By increasing the purging nitrogen pressure, oxygen concentration was attenuated, and increased post-encapsulation cell viability was achieved. A reaction-diffusion model was used to predict the cumulative intradroplet concentration of peroxy radicals, which corresponded directly to post-encapsulation cell viability. The nitrogen-jacketed microfluidic device presented here allows the droplet oxygen concentration to be finely tuned during cell encapsulation, leading to high post-encapsulation cell viability.


Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease.
The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD. Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years. Our results indicate two types of risks for those who attended the feast, a Feast Risk and a General Risk. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing. The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans.